Vutrisiran's benefit in ATTR cardiomyopathy did not differ detectably whether or not patients took tafamidis

Design

Secondary analysis of a randomised, double-blind, placebo-controlled trial (HELIOS-B)

Population

654 patients with transthyretin amyloid cardiomyopathy

Primary outcome

All-cause mortality and recurrent cardiovascular events, by concomitant therapy

Effect

No effect modification: P-interaction tafamidis 0.95, SGLT2i 0.59, MRA 0.92, beta-blocker 0.75, RAS inhibitor 0.82

HELIOS-B randomised 654 patients with transthyretin amyloid cardiomyopathy to vutrisiran, an RNA interference drug, or placebo, and showed fewer deaths and recurrent cardiovascular events. This secondary analysis asked whether background therapy changed that effect.

At baseline, 40% were on tafamidis and 77% on at least one heart failure drug. Mineralocorticoid receptor antagonists and SGLT2 inhibitors were the drugs most often started during follow-up, more so in the placebo arm. There was no evidence that tafamidis, SGLT2 inhibitors, MRAs, beta-blockers or renin-angiotensin inhibitors modified vutrisiran's effect (all interaction P values 0.59 to 0.95).

For clinicians, this means vutrisiran's result is not confined to patients on no other therapy. It does not show that combining vutrisiran with tafamidis is better than either alone; the trial did not test that.

• In HELIOS-B, there was no evidence that background tafamidis reduced the benefit of vutrisiran.
• Heart failure drugs, including SGLT2 inhibitors and MRAs, can be continued alongside vutrisiran.
• Whether a patient needs both a stabiliser and a silencer is still untested.
• In India, cost and access decide most ATTR-CM choices; neither drug is widely available at scale.

Why it matters

It removes one reason to hesitate over vutrisiran in patients already on standard therapy.

Don't overread it

The analysis does not show that combining vutrisiran with tafamidis adds benefit.

The statistics, in plain English

An interaction P value tests whether the treatment effect differs between groups. Values of 0.59 to 0.95 mean no evidence of a difference, but trials are rarely powered to detect one, so 'no evidence of difference' is not proof that combination adds nothing.

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